Synchrony between end of ventilator cycles and end of patient efforts during assisted ventilation

ABSTRACT

Automatic ongoing adjustment of the cycling-off time of ventilator inflation phase during assisted ventilation in accordance with true respiratory rate of a patient. Electrical signals are generated corresponding to the gas flow exchanged between patient and ventilator (flow) and/or to airway pressure (P aw ) and the true respiratory rate of the patient (patient RR) is determined on an ongoing basis from the flow and/or P aw . The current average cycle duration of patient respiratory efforts (current patient T TOT ) is estimated from patient RR. A current desirable duration of the inhalation phase (desirable T I ) is calculated from the product of current patient T TOT  a T I /T TOT  ratio chosen to be in the physiological range, usually 0.25 to 0.50. The ventilator phase is caused to terminate in accordance with the desirable T I .

REFERENCE TO RELATED APPLICATIONS

This application is a US National Phase filing under 35 USC 371 ofPCT/CA2004/000382 filed Mar. 15, 2004 which claims priority under 35 USC119(e) from U.S. Provisional Patent Application No. 60/454,533 filedMar. 14, 2003 and under 35 USC 120 from PCT/CA03/00976 filed Jun. 27,2003.

BACKGROUND TO THE INVENTION

In assisted ventilation, ventilator cycles are triggered by patientinspiratory efforts. There is no mechanism, however, to insure thatventilator cycles terminate at, or near, the end of inspiratory effort.Because the duration of patient inspiratory efforts (neural T_(I))varies over a wide range (0.5 to 2.5 seconds), the lack of a linkbetween end of ventilator and patient inspiratory cycles often resultsin ventilator cycles extending well beyond the inspiratory effort(delayed cycling off) or terminating before the end of inspiratoryeffort, forcing exhalation when the patient is still trying to inhale.The delayed cycling off in particular is often severe with theventilator cycle extending throughout the patient's expiratory phase(FIG. 1). Because such delayed cycling off interferes with lung emptyingduring the patient's expiratory phase, the next breath usually beginsbefore lung volume has returned to the neutral level. This delaysventilator triggering and often causes many patient cycles to beineffective in triggering the ventilator (ineffective efforts, FIG. 1).

Non-synchrony between patient and ventilator is extremely common. Leunget al found that, on average, 28% of patient's efforts are ineffective(Leung P, Jubran A, Tobin M J (1997), Comparison of assisted ventilatormodes on triggering, patient effort, and dyspnea. Am J Respir Crit CareMed 155:1940-1948). Considering that ineffective efforts are the extrememanifestation of non-synchrony, less severe, yet substantial, delaysmust occur even more frequently. Non-synchrony is believed to causedistress, leading to excessive sedation and sleep disruption, as well aserrors is clinical assessment of patients since the respiratory rate ofthe ventilator can be quite different from that of the patient (e.g.FIG. 1).

Cycling-off errors result from the fact that, except with ProportionalAssist Ventilation, current ventilator modes do not include anyprovision that links the end of ventilator cycle to end of patient'sinspiratory effort. In the most common form of assisted ventilation,volume-cycled ventilation, the user sets the duration of the inflationcycle without knowledge of the duration of patient's inspiratory effort.Thus, any agreement between the ends of ventilator and patientinspiratory phases is coincidental. With the second most common form,pressure support ventilation, the inflation phase ends when inspiratoryflow decreases below a specified value. Although the time at which thisthreshold is reached is, to some extent, related to patient effort, itis to the largest extent related to the values of passive resistance andelastance of the patient. In patients in whom the product[resistance/elastance], otherwise known as respiratory time constant, ishigh, the ventilator cycle may extend well beyond patient effort, whilein those with a low time constant the cycle may end before the end ofpatient's effort (Younes M (1993) Patient-ventilator interaction withpressure-assisted modalities of ventilatory support. Seminars inRespiratory Medicine 14:299-322; Yamada Y, Du H L (2000) Analysis of themechanisms of expiratory asynchrony in pressure support ventilation: amathematical approach. J Appl Physiol 88:2143-2150). The presentinvention concerns methods and devices to insure that the end of theventilator cycle does not deviate substantially from the end ofpatient's effort. This is achieved by insuring that the duration of theventilator's inflation phase is a physiologic fraction (0.25-0.50) ofthe patient's respiratory cycle duration (patient T_(TOT)). In thisfashion enough time is available for lung emptying during the patient'sexpiratory phase. By extension, this also reduces dynamic hyperinflationat the onset of patient efforts, thereby also minimizing trigger delaysand further improving synchrony.

In PCT/CA03/00976, filed Jun. 27, 2003, (WO 2004/002561), from whichthis application claims priority, I described an approach to generate asemi-quantitative estimate of the pressure waveform generated by thepatient's respiratory muscles. This waveform can be used to identify theonset and end of patient's efforts. According to the aforementionedinvention, the end of patient's inspiratory effort, detected by saidinvention, can be used to cycle off the ventilator, thereby insuringsynchrony between the ends of ventilator and patient's inspiratoryphases. There is, however, one potential complication to this approach.At times, end of patient effort occurs soon after ventilator triggering.This is because inspiratory muscle activity can be inhibited ifinspiratory flow is high, and the ventilator frequently deliversexcessive flow soon after triggering. Thus, this approach may result inmedically unacceptable inflation times. It was recommended that aback-up procedure be included to insure that the duration of inflationphase is physiologically appropriate. A number of approaches to insure aphysiologically appropriate duration of the inflation phase wereproposed. These were in part derived from a separate applicationconcerned specifically with methods to synchronize end of ventilatorcycle with end of patient effort that do not require knowledge of whensaid patient efforts end (U.S. provisional Application 60/454,533, Mar.14, 2003, from which this application claims priority). The currentapplication describes rationale and implementation of said methods indetail and, additionally, introduces other approaches described in theMar. 14, 2003 U.S. Provisional application (60/454,533) and not referredto in PCT/CA03/00976. The following is the rationale and method forensuring that the duration of the inflation phase remains withinphysiologic limits.

In spontaneously breathing subjects and patients, the duration of theinspiratory phase (T_(I)) ranges between 25% and 50% of respiratorycycle duration (T_(TOT)). In studies by the inventor using proportionalassist ventilation (PAV), with which the duration of the ventilator'sinflation phase mirrors the patient's own T_(I), the ratio of T_(I) toT_(TOT) (T_(I)/T_(TOT) ratio) was also found to be between 0.25 and 0.5.Therefore, one approach to insure that the duration of the inflationphase is within the physiologic range is to constrain the duration ofthe inflation phase to be between 0.25 and 0.50 of the total cycleduration of patient's own efforts (to be distinguished from duration ofventilator cycles). Implementation of this procedure requires knowledgeof the true respiratory rate of the patient (as opposed to ventilatorrate). The inventor, in association with his students and technicians,described a method for visually determining true patient rate byidentifying visually distinctive patterns in the waveforms ofrespiratory flow and airway pressure (Giannouli et al, American Journalof Respiratory and Critical Care Medicine, vol 159, pages 1716-1725,1999). According to this approach, true patient rate is the sum ofventilator rate, the number of ineffective efforts occurring during theventilator's exhalation phase (arrows marked “c”, FIG. 1) and the numberof additional efforts occurring during inflations triggered by anearlier effort (arrows marked “b”, FIG. 1). In PCT/CA03/00976 ventilatorcycles triggered by patient (arrows “a”, FIG. 1) as well as ineffectiveefforts occurring during exhalation (arrows “b”, FIG. 1) are to beautomatically detected from the new composite signal generated from theflow, P_(aw) and volume signals. In the present invention, I describeanother approach for identifying ineffective efforts. An approach wasdescribed in PCT/CA03/00976 to identify additional efforts occurringduring the inflation phase (arrows “c”, FIG. 1). This approach isretained here with minor modifications.

As indicated in U.S. Provisional application 60/454,533, and also inPCT/CA03/00976, once the true respiratory rate of patient is known, itbecomes possible to calculate the real duration of respiratory cycles ofthe patient (T_(TOT)=60/respiratory rate) and determine the range ofinflation times consistent with a physiologic T_(I)/T_(TOT). Forexample, if patient's rate is 30/min, T_(TOT) is 2.0 seconds and thephysiological range for the inflation phase is 0.5-1.0 second reflectinga T_(I)/T_(TOT) range of 0.25 to 0.50. The desirable duration of theventilator's inflation phase is then determined by multiplying patientT_(TOT) by a user selected physiologic T_(I)/T_(TOT) ratio or a suitabledefault value (e.g. 0.4). The ventilator's inflation phase can then bemade to cycle off after said desirable duration.

There are a number of ways by which the duration of the ventilator'sinflation phase can be made to correspond to desirable T_(I). Oneapproach, discussed in U.S. Provisional application 60/454,533 and alsoproposed in PCT/CA03/00976, is to terminate the inflation phase at thespecified desirable duration following onset of inspiratory effort orfollowing the time of ventilator triggering. With this approachventilator inflation varies strictly with average respiratory ratediscerned from a number of elapsed breaths. There is no provision,therefore, for accommodating breath-by-breath changes in duration ofinspiratory effort since the desirable duration is predetermined beforethe effort begins (based on an average result obtained from a number ofelapsed breaths). Another approach, particularly suited for pressuresupport ventilation, is to retain the usual criterion for terminatingthe inflation phase, namely when inspiratory flow reaches a specifiedthreshold, but flow threshold is adjusted to produce the desired T_(I).This would permit breath-by-breath changes in patient's T_(I) toinfluence ventilator T_(I) in current breaths but ventilator T_(I)would, on average, correspond to desirable T_(I). This general approachwas proposed in U.S. Provisional application 60/454,533. InPCT/CA03/00976 I proposed that this general approach be implemented bymeasuring the flow occurring at the desirable T_(I) in a number ofelapsed breaths. This would then become the flow threshold forterminating the inflation phase in prospective (i.e. current) breaths.An alternative approach proposed in U.S. Provisional application60/454,533 (but not in PCT/CA03/00976) is to measure actual ventilatorT_(I) in a number of elapsed breaths. This actual value is compared withdesirable T_(I) with the difference (i.e. actual T_(I)−desirable T_(I))representing an error signal that can be used for closed-loop control ofthe flow threshold for cycling off, using any of a number of closed-loopcontrol approaches. Alternatively, the error signal can be thedifference between actual T_(I)/T_(TOT) (i.e. actual T_(I)/patientT_(TOT)) and desirable T_(I)/T_(TOT).

In my experience, patient's respiratory rate often changes substantiallyfrom time to time. An essential feature of this invention is, therefore,the provision for automatic means to monitor patient respiratory rateand to update the relevant values (e.g. desirable T_(I), actual T_(I),T_(I) error . . . etc) at frequent intervals.

With current methods of assisted ventilation tidal volume is directlyrelated to the duration of the inflation phase. Changes in the durationof the inflation phase produced by the methods of the current inventionare, therefore, expected to result in corresponding changes in tidalvolume. In another aspect of the current invention provision is made topartially or completely offset the resulting changes in tidal volume byconcomitantly increasing inspiratory flow (in the case of volume-cycledventilation) or the support pressure (in the case of pressure support orassist/pressure control ventilation) when the duration of the inflationphase is decreased, and vice versa.

SUMMARY OF INVENTION

In summary, this invention concerns a novel approach for cycling offventilators in which the duration of the inspiratory phase isconstrained to be a physiological fraction (0.25 to 0.50) of theduration of patient breathing cycles (patient T_(TOT)). One aspect ofthe invention is the provision of means for ongoing automaticdetermination of patient T_(TOT) from the flow and/or airway pressuresignals. In another aspect, control of cycling off time in pressuresupport ventilation is effected by measuring the difference betweenactual and desirable T_(I) and using this error signal (differencebetween actual and desirable T_(I)) to determine the flow threshold forcycling off using closed loop control methods. In still another aspectof the invention, the level of delivered flow or pressure during theinflation phase is altered in concert with changes in ventilator T_(I)so as to partially or completely offset the changes in tidal volume thatwould result from uncompensated changes in the duration of the inflationphase.

In accordance with one aspect of the present invention, there isprovided a method for automatic ongoing adjustment of the cycling-offtime of ventilator inflation phase during assisted ventilation inaccordance with true respiratory rate of a patient, comprisinggenerating electrical signal(s) corresponding to rate of gas flowexchanged between patient and ventilator (flow) and/or to airwaypressure (P_(aw)), determining true respiratory rate of patient (patientRR) on an ongoing basis from the flow and/or P_(aw) signals, estimatingcurrent average cycle duration of patient respiratory efforts (currentpatient T_(TOT)) from the patient RR, calculating a current desirableduration of the inhalation phase (desirable T_(I)) from the product ofcurrent patient T_(TOT) and a T_(I)/T_(TOT) ratio chosen to be in thephysiological range (usually 0.25 to 0.50) and causing ventilatorinflation phase to terminate in accordance with the desirable T_(I).

In accordance with a further aspect of the present invention, there isprovided a device for automatic ongoing adjustment of the cycling-offtime of ventilator inflation phase during assisted ventilation inaccordance with true respiratory rate of the patient, comprisingcircuitry for generating electrical signal(s) corresponding to the flowexchanged between patient and ventilator (flow) and/or to airwaypressure (P_(aw)), digital or analog circuitry means for determiningtrue respiratory rate of patient (patient RR) on an ongoing basis fromthe flow and/or P_(aw) signals, digital or analog circuitry means forestimating current average cycle duration of patient respiratory efforts(current patient T_(TOT)) from the patient RR, digital or analogcircuitry means for calculating a current desirable duration of theinhalation phase (desirable T_(I)) from the product of current patientT_(TOT) and a T_(I)/T_(TOT) ratio chosen to be in the physiologicalrange (usually 0.25 to 0.50), and means to cycle off ventilatorinflation phase in accordance with the desirable T_(I).

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 contains tracings showing flow and airway pressure in aventilated patient, along with diaphragm pressure to indicate patient'sown efforts. Arrows marked “a” denote efforts that triggered ventilatorcycles. Arrows marked “b” indicate efforts that occurred in theexhalation phase but failed to trigger the ventilator (ineffectiveefforts). Arrows marked “c” denote extra efforts that occurred duringthe same ventilator inflation phase triggered by an earlier effort(additional efforts).

FIG. 2 contains tracings showing a method of detecting ineffective (IE)and additional (AE) efforts from the derivative of the flow signal(Δflow/Δt).

FIG. 3 is a block diagram of the preferred embodiment of digitalimplementation of the present invention.

FIGS. 4 to 13 are flow charts of the different functions listed in theblock diagram of FIG. 3.

DESCRIPTION OF THE PREFERRED EMBODIMENT OF THE INVENTION

A digital implementation of a preferred embodiment of the invention willbe described here (FIG. 3) because the method of the invention isprimarily intended for incorporation in microprocessor-basedventilators. As such, the method can be installed in a free-standingmicroprocessor that interacts with the ventilator's control circuitry ormay be fully incorporated in the ventilator's resident computer. It isrecognized, however, that most of the functions described here can beimplemented using standard analog circuits.

The basic hardware requirements (microprocessor, 1) are a CentralProcessing Unit (CPU, 2), Random Access Memory (RAM, 3) and Read OnlyMemory (ROM, (4)).

A. Inputs:

It is assumed here that inputs are in digital form. If some or all areavailable only in analog form, an analog to digital converter (notshown) must be installed upstream from the CPU to receive and digitizethe analog inputs.

Inputs may vary depending on user preference and independentavailability, within the host ventilator, of signals required forimplementation of the present invention. In the preferred embodimentillustrated in FIG. 3 (5), it is assumed that the device of the presentinvention will be responsible for determining patient's respiratory ratebut that signals corresponding to onset and end of ventilator breathsare already available from the host ventilator. Modifications to thisarrangement will be described at the appropriate locations below.

A.1 Inputs Corresponding to Flow (6) and/or Airway Pressure (P_(aw), 7):

Virtually all modern ventilators monitor air flow within the ventilatorcircuit and generate a signal corresponding to the rate of gas flowexchanged between patient and ventilator. Furthermore, airway pressure(P_(aw)) is routinely monitored. These resident signals can be used asinputs to the microprocessor implementing the current invention.Alternatively, if the present invention is incorporated in an externaldevice, flow and P_(aw) signals can be generated independently bystandard techniques (for example, as described in PCT/CA03/00976).

Flow (6) and P_(aw) (7) signals are used to determine a) patient'srespiratory rate and b) to implement a specific method (custom changefunction) of closed loop control of “cycling-off” flow threshold in thepressure support mode (see B.2.2.4, below). In the event patient'srespiratory rate is determined from only one of these signals (forexample, flow only or P_(aw) only) and a different method of closed loopcontrol of “cycling-off” flow threshold is used, the other input can beomitted.

A.2 Mode (8):

The present invention is primarily intended for use when the ventilatoris in the pressure support mode (PSV). It can, however, also be used inthe assist/control modes (A/C). Because implementation of this inventionvaries with the mode used (see FUNCTIONS, below), an input reflectingthe mode being used is recommended. When the current invention isincorporated within the ventilator, this input can be obtained directlyfrom the ventilator's control system. Alternatively, if the invention isincorporated in an external device (for example, as described inPCT/CA03/00976), the mode of ventilation is entered by the user.

A.3 T_(on) (9):

This is a signal that indicates either the time of onset of patientinspiratory effort or the time of onset of a ventilator inflation cycledepending on which is available. In practice, if the present inventionis implemented, dynamic hyperinflation is minimized and there should belittle difference between the two times (i.e. trigger delay should beminimal). In all current ventilators, the ventilator control systemgenerates a triggering signal that initiates a ventilator cycle. Thissignal can be used as T_(on) (9). Ventilator cycles can be triggeredeither in response to patient effort (patient-triggered cycles) or bythe ventilator itself if a triggering effort did not occur within a timespecified by a user-selected back-up rate (ventilator-triggered cycles).Ventilators can distinguish between these two types of triggers. If theventilator's trigger signal is to be used as T_(on), only the signalsrelated to patient-triggered cycles are communicated to themicroprocessor implementing the current invention. If the currentinvention is implemented in an external device (i.e. the ventilator'strigger signals are not available), the onset of ventilator cycle can beidentified externally from the pressure and/or flow signal using any ofa number of obvious techniques (for example, as described inPCT/CA03/00976).

According to recent developments (PCT/CA03/00976), onset of patientinspiratory effort can be identified non-invasively. Suchdevices/methods may be incorporated in future ventilators or be used asexternal devices. In either case, the onset of patient inspiratoryeffort identified by such device/method, or by other means available tothe ventilator, can be used as T_(on) for the sake of the currentinvention.

A.4 T_(off) (10):

This is a signal that indicates the end of the ventilator's inflationphase. It can be obtained directly from the ventilator's control system(cycling-off signal) or be derived independently from the flow (6)and/or P_(aw) (7) signal using any of a number of obvious methods (forexample, as described in PCT/CA03/00976).

A.5 Desired T_(I)/T_(TOT) Ratio (11):

This ratio is preferably a user-selected input that would normally rangebetween 0.25 and 0.50. Alternatively, it can be replaced by a defaultvalue. A default value of 0.4 would be appropriate, but other valuespreferred by manufacturers may be used instead. One embodiment is tolink the default T_(I)/T_(TOT) to patient respiratory rate with highdefault ratios being used when patient rate is high, and vice versa.This would preclude having very short T_(I) when patient rate is veryhigh and very long T_(I) when rate is slow. A suggested relation is touse a default ratio of 0.5 when rate is 50 min⁻¹ and a ratio of 0.3 whenrate is 10 min⁻¹, with intermediate values for intermediate rates.

B. Functions:

B.1 Real-Time Functions:

The timed interrupt request process (Timed IRQ process, 12) is executedat suitable intervals (for example, every 5 msec). This collects datafrom various inputs (see FIG. 3 for inputs), calculates the timederivative of flow and stores collected and derived data in memory. Thisalso checks for the times at which T_(on) and T_(off), occur and storesthem in memory.

B.2 Non Real-Time Functions:

B.2.1 Power ON Start-Up Routine (13):

The power on start-up routine clears the memory and enables theInterrupt Request (IRQ) Process.

B.2.2 Functions to Determine Patient Respiratory Rate:

As indicated in the Background section above, patient's respiratory ratemay be quite different from ventilator's rate (for example, FIG. 1). Itis the patient's rate that needs to be known in order to set theventilator's inflation time to be in the physiological range.Furthermore, since patient's rate may vary considerably from time totime, it is necessary to monitor patient's rate on an ongoing basis. Inthis preferred embodiment (1), I have developed an automatic continuousdigital approach based on the visual (identified by eye) approachdescribed by Giannouli et al (Am. J. Respir. Crit. Care Med. 159:1716-1725, 1999). This approach is described here only to illustratethat patient rate can be monitored automatically on an ongoing basisusing simple processing of universally available signals (flow and/orP_(aw)). There are a number of other approaches that can be employed toachieve the same end. For example, a signal combining flow, volume andP_(aw) can be generated from which true respiratory rate can beestimated, as described in PCT/CA03/00976. Alternatively, although suchmethods have not yet been specifically described, it may be possible toobtain patient's rate by spectral analysis of the flow and/or P_(aw)signal (looking for the frequency of significant power peaks in therespiratory rate range (10 to 50 min⁻¹)) or by other mathematicalanalyses of these signals. Furthermore, it is theoretically possible toestimate patient rate from signals other than flow and/or P_(aw), forexample from changes in electrical impedance or inductance of the chestwall, from strain gauges placed on the chest wall, or from monitoringelectrical activity of respiratory muscles. Other methods may bedeveloped in the future to estimate patient's rate. The specific way bywhich patient rate is continuously monitored is not the subject of thecurrent patent application. Where methods other than the one describedhere are used to continuously monitor patient's rate the result of suchdetermination can be inputted directly in the microprocessor of thepresent invention.

In the approach used in the preferred embodiment (1), patient's rate isestimated from the sum of a) patient triggered ventilator cycles (“a”arrows, FIG. 1), b) respiratory efforts occurring during theventilator's exhalation phase that did not trigger ventilator cycles(ineffective efforts, “b” arrows, FIG. 1), and c) additional inspiratoryefforts occurring during the ventilator's inflation phase (additionalefforts, “c” arrows, FIG. 1). Patient triggered ventilator cycles(T_(on)) are identified by the IRQ process (12) and stored in memory.Separate functions are included for detection of ineffective efforts(16) and additional efforts (18). A fourth function (20) sums the 3results over specified elapsed intervals to obtain patient's rate/minuteand average patient cycle duration (patient T_(TOT)). Beforeimplementing these functions it is desirable to determine the time ofoccurrence of peak inspiratory and expiratory flow.

B.2.2.1 Peak Inspiratory Flow Function (14):

This function determines the magnitude and time of occurrence of maximumflow during the inflation phase in each elapsed ventilator cycle. Itsearches the flow signal between T_(on) and T_(off) of the precedinginflation phase looking for the highest value and stores the actual flowvalue and its time.

B.2.2.2 Peak Expiratory Flow Function (15):

This function determines the magnitude and time of occurrence of peakexpiratory flow during the expiratory phase in each elapsed ventilatorcycle. It searches the flow signal between T_(off) and the next T_(on)looking for the lowest value and stores the actual flow value and itstime.

B.2.2.3 Ineffective Efforts Function (16):

This function searches the flow signal of each elapsed exhalation phasein the interval between peak expiratory flow (15) and next T_(on) (9)for evidence of efforts that did not trigger a ventilator cycle. FIG. 2shows the principle of the preferred approach described herein. FIG. 2shows tracings of airway pressure (P_(aw)), flow, rate of change in flow(Δflow/Δt) and diaphragm pressure. An ineffective effort occurred at thearrow (arrows marked IE). In the passive state, once expiratory flowreaches its peak value, it should progressively decrease (i.e. flowbecomes less negative) until the next ventilator cycle. This shouldresult in a continuously positive Δflow/Δt signal. When an inspiratoryeffort occurs, expiratory flow initially moves toward zero at a fasterrate (and flow may become transiently positive, FIG. 2). If the effortends without triggering the ventilator, as illustrated in FIG. 2 (arrowmarked IE), expiratory flow increases again (i.e. flow becomes morenegative). After reaching a maximum value, expiratory flow beginsdecreasing again toward zero and continues to do so until the nextinspiratory effort. This sequence results in a characteristic pattern inthe Δflow/Δt signal. The signal rises at a faster rate than before withthe onset of effort. Then the signal declines transiently into thenegative range (point “a”, FIG. 2) and finally crosses zero again intopositive range (point “b”, FIG. 2). During passive expiration, Δflow/Δtshould not become negative except very briefly in association withtransient noise, such as secretions or tube vibrations. Such artifactualnegative transients have much shorter durations than ineffective efforts(see arrows marked “noise” in FIG. 2). Accordingly, identification ofineffective efforts in this preferred embodiment of the invention isbased on detecting negative transients in the Δflow/Δt signal having aduration that is greater than that of the usual noise. From experience,I found that a negative transient duration of approximately 0.15 secondprovides a good separation between noise and ineffective efforts. Twoother optional conditions are implemented in the preferred embodimentthat, based on experience, minimize false identification of ineffectiveefforts: a) requiring that flow at the onset of the negative transientin Δflow/Δt (point “a”, FIG. 2) be higher than flow at the end of thetransient (point “b”, FIG. 2) by a specified amount. In FIG. 2, thedifference in flow between the two points was 0.4 l/second. A minimumdifference of 0.075 l/second is recommended. Note that a second negativetransient related to noise did not meet this criterion, (b) requiringthat P_(aw) at the onset of the negative transient in Δflow/Δt point“a”, FIG. 2) be lower than P_(aw) at the end of the transient (point“b”, FIG. 2). When an ineffective effort is identified, its time isstored in memory. From this, the number of ineffective efforts perminute can be calculated and displayed (17).

During the exhalation phase P_(aw) is a function of expiratory flow andresistance of the exhalation tube/valve combination. Accordingly,changes in flow produce corresponding changes in P_(aw); when expiratoryflow decreases (i.e. becomes less negative) P_(aw) also decreases (i.e.becomes less positive) (for example, note that P_(aw) during exhalationis a mirror image of flow, FIG. 2). For this reason, detection ofineffective efforts can be made from the P_(aw) signal using a similarapproach to that described above for flow. P_(aw) is differentiated(ΔP_(aw)/Δt). A positive transient in ΔP_(aw)/Δt of sufficient width,and associated with a threshold increase in P_(aw), would indicate anineffective effort. In my experience, however, use of flow signal ispreferable since changes in P_(aw) associated with ineffective effortscan be quite subtle, particularly when exhalation line resistance islow.

B.2.2.4 Additional Efforts Function (18):

This function detects additional efforts occurring during the inflationphase and is applicable only in pressure-cycled modes (for example, PSV,pressure control). The principles employed are similar to those forineffective effort detection (16). In pressure-cycled modes, onceinspiratory flow reaches its peak value it should progressively declinetowards zero. A secondary increase of sufficient duration occurringduring the same inflation invariably indicates an additional effort(Giannouli et al, Am. J. Respir. Crit. Care Med. 159: 1716-1725, 1999).This pattern results in a characteristic change in Δflow/Δt (FIG. 2).Δflow/Δt is negative early in the inflation phase, beyond peak flow, asexpected. However, instead of remaining negative until the end of thephase, it becomes positive (point “c”, FIG. 2) for a while beforebecoming negative again point “d”, FIG. 2). In the preferred embodiment,additional efforts are identified if there are positive transients inΔflow/Δt between the time of peak inspiratory flow and T_(off). Toeliminate artifactual positive transients related to non-specific noise,two additional optional requirements are specified: a) Flow at the endof the positive Δflow/Δt transient (point “d”, FIG. 2) should be higherthan flow at the onset of the transient (point “c”, FIG. 2) by aspecified amount. In the illustrated example it was higher by 0.2l/second. A minimum required value of 0.05 l/sec is suggested. b) Thedifference between instantaneous flow beyond point “c” and flow at point“c” is integrated between point “c” and T_(off) (shaded area). Theintegral should exceed a specified value. A value of 0.03 l issuggested. When an additional effort is identified its time is stored inmemory. From this, the number of additional efforts per minute can becalculated and displayed (19).

B.2.2.5 Patient Rate/T_(TOT) Function (20):

This function simply adds all events identified as T_(on) (by the IRQprocess (12)), ineffective efforts (identified by ineffective effortsfunction (16)) and additional efforts (identified by additional effortsfunction (18)) stored in memory over a specified period. The specifiedperiod may be 1.0 minute, or any other interval selected by manufactureror user. A preferred approach (20) is to count all events identifiedover an interval corresponding to a specified number of ventilatorcycles (e.g. 10 ventilator cycles). From this, average patient rate iscalculated from [(number of events*60)/(period covered by specifiednumber of ventilator cycles)]. Patient T_(TOT) is then calculated from[60/patient rate]. Patient rate and average T_(TOT) values are updatedat suitable intervals, preferably after each elapsed ventilator cycle.Patient rate and/or average patient T_(TOT) may be displayed (21).

At times in the assist/control modes the patient is apneic, there beingno respiratory efforts, effective or not. Likewise, at times in thepressure support mode, the patient develops recurrent periods of centralapnea during which there are no efforts. Inclusion of these apneicperiods in the calculation of average patient rate/T_(TOT) would resultin substantial underestimation in the respiratory rate of the patientwhen he/she is making respiratory efforts. By extension, this errorwould result in overestimation of patient T_(TOT) when patient is makingrespiratory efforts. A number of approaches can be implemented to avoidthis error. For example, periods in excess of a specified duration (forexample, 10 seconds) during which there were no efforts of any kind(i.e. effective, ineffective or additional) are excluded from analysis.In another approach, the intervals between successive efforts (whetherthey triggered the ventilator (as indicated by T_(on)), were ineffectiveor additional) are tabulated. Intervals exceeding the normal variance ofthis variable (for example, >mean+2 standard deviations) are excludedfrom analysis of patient respiratory rate/T_(TOT).

B.2.3 Functions to Calculate Ventilator T_(I) Error:

B.2.3.1 Desirable T_(I) Function (22):

This calculates the ventilator inflation phase duration that wouldresult in a physiologically desirable T_(I)/T_(TOT). Desirable T_(I) isestimated from patient current average T_(TOT) value (20) and thedesirable T_(I)/T_(TOT) ratio, with the latter being either a userselected value (11) or a default value (see A.5). Because patientcurrent average T_(TOT) value (20) is updated continuously at suitableintervals, desirable T_(I) is automatically updated at the sameintervals, preferably after each elapsed ventilator cycle. DesirableT_(I) is communicated to the ventilator (23) for use to adjustventilator T_(I) or for display to the user. It is recommended that aminimum (e.g. 0.5 second) and a maximum (e.g. 2.5 second) be assigned tothis value.

B.2.3.2 Actual T_(I) Function (24):

This calculates the average duration of inflation phase of a suitablenumber of elapsed ventilator cycles. Ventilator T_(I) is calculated foreach elapsed breath from the difference between T_(on) and T_(off) ofthat breath. Results of individual breaths are stored in a buffer.Actual T_(I) is the average of such values over a suitable number ofelapsed breaths. This number should ideally be the same as the numberused to estimate average patient T_(TOT) (20). In the preferredembodiment, the number is 10 breaths. Actual T_(I) is updated atsuitable intervals, preferably after each elapsed ventilator cycle.

B.2.3.3 T_(I) Error Function (25):

This function calculates the average difference between actual (24) anddesirable (22) T_(I). An alternate format is to calculate the differencebetween actual and desired T_(I)/T_(TOT) with the former calculated fromactual T_(I) (24)/patient T_(TOT) (20). T_(I) error is updated atsuitable intervals, preferably after each elapsed ventilator cycle.T_(I) error is communicated to the ventilator (26) for use to adjustventilator T_(I) or for display to the user.

B.2.4 Functions for the Control of Ventilator Cycling-Off Time:

There are a number of ways by which the output of the aforementionedfunctions can be used to continuously adjust ventilator cycling in orderto obtain a desirable T_(I)/T_(TOT). The choice would clearly be up tothe ventilator manufacturer. Only a few examples of possible approachesare discussed here.

In the assist/control modes, the desirable T_(I) output (23) can be usedto continuously update the programmed ventilator cycle duration(ventilator T_(I)) in the ventilator's control circuitry. In thisfashion, ventilator T_(I) changes continuously and appropriately inresponse to spontaneous changes in patient rate, which are quitefrequent. Because in the volume cycled mode tidal volume is directlyrelated to ventilator T_(I), changes in the latter induced by thecurrent invention will necessarily result in similar changes indelivered tidal volume. This may be desirable in some cases in that anincrease in patient rate, with a consequent reduction in ventilatorT_(I), would result in a reduction in tidal volume, maintainingventilation approximately the same and avoiding over-ventilation. Someusers, however, may prefer to partially or completely avoid changes intidal volume in response to changes in respiratory rate. In this case,an option may be provided whereby a decrease in ventilator T_(I) isautomatically offset by appropriate and simultaneous increase in flowrate, and vice versa. The adjustment in flow rate can be designed tocompletely or only partially offset the change in tidal volume resultingfrom the change in ventilator T_(I). For example, the simultaneous %change in flow rate can be set to be a fraction of the % change inventilator T_(I) with said fraction being user-specified or a defaultvalue (for example, 50%, 60% etc).

Frequently, the duration of patient inspiratory effort varies frombreath to breath. In this case, the use of a ventilator T_(I),corresponding to an estimated average patient T_(I), may result in theventilator cycling off before the end of inspiratory effort in somebreaths. In another aspect of this invention, the implemented ventilatorT_(I) corresponds to the desirable T_(I) generated by the currentinvention (23) plus a specified amount (for example, 0.2 sec) orspecified fraction (for example, 10% etc). In this fashion, thefrequency of cycles in which the ventilator inflation phase terminatesbefore patient effort is reduced. The increase, over desirable T_(I), tobe implemented may be a user input or a default value. It is readilypossible to identify cycles in which the ventilator breath terminatedprematurely from observing the flow pattern on the ventilator screen.The adjustable incremental amount to be used can, accordingly, be set bythe user to minimize the occurrence of such events.

The same approach can be used to cycle off the ventilator in thepressure support mode. Thus, instead of the conventional flow-basedcycling-off mechanism, the ventilator can be made to cycle off at thedesirable T_(I) identified by the present invention (23). An option toalter the pressure level simultaneously, as desirable T_(I) changes, mayalso be provided to partially or completely offset the changes in tidalvolume resulting from the different T_(I). Additionally, an option toincrease the desirable T_(I) (23) by a specified amount or percent (asin the case of volume cycled ventilation described above) beforeimplementation can be provided to minimize instances of ventilator cycleterminating before patient effort.

An alternative and preferred approach, however, is to retain theflow-based cycling-off mechanism and utilize the results of the currentinvention to continuously adjust the flow threshold for cycling off. Byretaining the flow-based cycling-off mechanism, spontaneous changes induration of patient inspiratory effort continue to influence ventilatorT_(I), since a longer patient T_(I) will delay the point at which theflow threshold is reached, and vice versa. However, the presentinvention can provide the flow threshold that will result in a desirableT_(I)/T_(TOT).

There are several approaches by which the results of the currentinvention can be used to continuously adjust the cycling-off flowthreshold in order to obtain a desirable T_(I)/T_(TOT) ratio (closedloop control of flow threshold). Four such functions are described here.All functions utilize the T_(I) error signal (26) to effect changes inflow threshold. The ventilator manufacturer may select one of them orutilize some other control paradigm of his choice. It is recognized thatbecause of the spontaneous breath-by-breath differences in patientT_(TOT) and T_(I), feedback should not operate on a breath-by-breathbasis. Rather, the average error calculated over a number of elapsedbreaths should be used, as done here (25). Furthermore, because it isnot clinically critical to rapidly adjust the flow threshold, feedbackwith slow response is preferred to avoid instability.

B.2.4.1 Fixed Change Function (27):

In this approach, a fixed increment or decrement in flow threshold isimplemented depending on magnitude and polarity of the T_(I) errorsignal (25). For example, if −0.1<T_(I) error<0.1, no change isimplemented. If T_(I) error>0.1 second, flow threshold is increased by afixed amount and if it is <−0.1 second, threshold is decreased by afixed amount. A value of 0.05 l/second is used in the illustratedembodiment (27) but other values can obviously be used. The larger thestep change, the faster the response but the more likely it is for thesystem to overcorrect and have an oscillatory response. Because the fulleffect of the implemented change on T_(I) error will not become apparentuntil a number of breaths have elapsed (since the T_(I) error (25) isbased on average of a number of breaths) step changes in flow thresholdare computed only every “n” breaths, where “n” is the number of breathsused in calculating T_(I) error (25) (see Main Program Loop Function(33). In the preferred embodiment, I have used n=10 (33).

B.2.4.2 Custom Change Function (28):

Here the recommended change in flow threshold is based on the averagerate of change in flow in the terminal part of the inflation phase in asuitable number of elapsed breaths. To determine the flow VS time slope,flow at T_(off) and at a suitable interval before T_(off) is measured ina suitable number of elapsed breaths. The difference between averageflow at the two points divided by the interval between the two points ofmeasurement provides the relevant slope. In the preferred embodiment(28), I have used an interval of 0.2 second and 10 elapsed breaths. Therecommended change in flow threshold is then calculated from T_(I)error*calculated slope. Because the flow VS time relation in pressuresupport ventilation is usually not linear, the calculated slope over anarbitrarily selected interval may not be representative of the slopebefore or after this interval. For this reason, it is prudent not toapply the recommended change (from T_(I) error*calculated slope) all atonce. In the preferred embodiment (28), the recommended change ismultiplied by an attenuation factor (e.g. 0.5). This will slow thecorrection somewhat but will improve stability. Other attenuationfactors may be used depending on manufacturer preference. An alternativeapproach (not illustrated) is to fit the flow VS time relation inelapsed breaths with a non-linear function and calculate the requiredchange in flow threshold from T_(I) error (25) and said non-linearfunction.

As in the case of the fixed change function (27), because the fulleffect of the implemented change on T_(I) error will not become apparentuntil a number of breaths have elapsed (since the T_(I) error (25) isbased on average of a number of breaths) custom changes in flowthreshold are computed only every “n” breaths where “n” is the number ofbreaths used in calculating T_(I) error (25). (see Main Program LoopFunction (33).

B.2.4.3 Hybrid Change Function (29):

Although the custom change function (28) should, on average, result infaster correction than the fixed change function (27), at times flow isquite flat over short intervals near the end of the inflation phase. Inthis case, the custom function (28) would result in very smallrecommended changes. In the hybrid function, the changes recommended byboth the fixed (27) and custom (28) functions are calculated and the onewith the higher absolute value is used. The hybrid function is executedat the same time the other two functions are executed (i.e. every “n”breaths). The hybrid function is preferred for general use and itsoutput is the one utilized in the preferred embodiment (see Timed IRQprocess (12)). However, the result of the fixed (27) or custom (28)functions may be the preferred output under some circumstances.

Based on manufacturer preference, the recommended change in flowthreshold, as derived from any of the above three functions (27-29), canbe outputted (30) in l/second or as % peak inspiratory flow. For thesake of the latter expression, the recommended change is divided by peakinspiratory flow obtained from the peak inspiratory flow function (14).The recommended change can then be added to or subtracted from the flowthreshold value currently stored in the ventilator's control system.Alternatively, the recommended change can be added to the average valueof flow at T_(off) (obtained from the custom change function (28)),which is an approximation of the current flow threshold, and the resultis expressed (30) as recommended flow threshold, as opposed torecommended change in flow threshold. This, again, can be expressedeither in l/second or as % peak flow according to manufacturerpreference.

B.2.4.4 Proportional/Integral/Derivative (PID) Function (31):

Here, rather than computing a recommended change in flow threshold, asdone by the above three functions (27 to 29), flow threshold is directlycontrolled by the T_(I) error function (25) using the standard PIDapproach. A composite error signal with three components is generated(31) from the T_(I) error signal (26). One component is proportional toT_(I) error (26), the other is proportional to the integral of T_(I)error (26) and the third is proportional to the derivative of T_(I)error (26). The gains of the individual components are adjusted foroptimal performance. This composite error signal (32) is then used forongoing adjustment of flow threshold for cycling off.

With all methods described above for closed-loop control of flowthreshold (27,28,29,31) it is recommended that the ventilatormanufacturer place a limit on how low the flow threshold for cycling offcan go. This will prevent instances of cycling off being preventedbecause of positive offsets in the ventilator's flow signal. Themagnitude of this set minimum value will clearly depend on the qualityof the ventilator's flow signal (i.e. tendency to drift . . . etc).

B.2.5 Main Program Loop Function (33):

This function is initiated with every T_(off.) It then executes thevarious functions in the appropriate order at a fixed point in thebreath cycle to guarantee the availability of all necessary variables.

Detailed flowcharts of the various functions used in the preferredembodiment are shown in FIGS. 4 to 13.

SUMMARY OF DISCLOSURE

In summary of this disclosure, the present invention provides method andapparatus for automatic ongoing adjustment of the cycling-off time ofventilator inflation phase during assisted ventilation in accordancewith true respiratory rate of the patient. Modifications are possiblewithin the scope of this invention.

1. A method for automatic ongoing adjustment of the cycling-off time ofventilator inflation phase during assisted ventilation in accordancewith true respiratory rate of a patient, comprising: generatingelectrical signal(s) corresponding to rate of gas flow exchanged betweenpatient and ventilator (flow) and/or to airway pressure (P_(aw));determining true respiratory rate of patient (patient RR) on an ongoingbasis from said flow and/or P_(aw) signals; estimating current averagecycle duration of patient respiratory efforts (current patient T_(TOT))from said patient RR; calculating a current desirable duration of theinhalation phase (desirable T_(I)) from the product of current patientT_(TOT) and a T_(I)/T_(TOT) ratio chosen to be in a physiological range;and causing ventilator inflation phase to terminate in accordance withsaid desirable T_(I).
 2. The method of claim 1 wherein ongoing patientRR is estimated from the sum of patient-triggered ventilator cycles,ineffective efforts during exhalation and additional efforts during theventilator's inflation phase.
 3. The method of claim 2 whereinineffective efforts are estimated from the derivative of the flow signal(Δflow/Δt), and identifying negative transients in said signal that meetspecified duration criteria, and/or from the derivative of the P_(aw)signal (ΔP_(aw)/Δt) and identifying positive transients in said signalthat meet specified duration criteria.
 4. The method of claim 1 whereinongoing patient RR is determined from a composite signal incorporatingboth flow and P_(aw).
 5. The method of claim 1 wherein ongoing patientRR is determined by spectral analysis of the flow and/or P_(aw) signal.6. The method of claim 1 wherein ongoing patient RR is determined fromelectrical inductance or impedance of the chest wall, strain gaugesplaced on chest wall, or from signals measuring electrical activity ofrespiratory muscles.
 7. The method of claim 1 wherein periods of centralapnea are excluded when estimating patient RR and patient T_(TOT). 8.The method of claim 1 wherein a minimum and/or maximum limit is placedon the calculated desirable T_(I).
 9. The method of claim 1 wherein theT_(I)/T_(TOT) ratio to be used in calculating desirable T_(I) is a userinput.
 10. The method of claim 1 wherein the T_(I)/T_(TOT) ratio to beused in calculating desirable T_(I) is a default value or a defaultfunction of patient RR.
 11. The method of claim 1 wherein calculateddesirable T_(I) is used to directly determine the duration of theinflation phase of the ventilator (ventilator T_(I)).
 12. The method ofclaim 11 wherein ventilator T_(I) is set to equal desirable T_(I) plus aspecified amount or a specified percent.
 13. The method of claim 1wherein actual T_(I) is also determined in a number of recently elapsedbreaths from the difference between cycling off time and either triggertime or time of onset of inspiratory effort, and a T_(I) error signalcorresponding to the difference between actual and desirable T_(I) isgenerated.
 14. The method of claim 13 wherein said T_(I) error signal isused to adjust the flow threshold for cycling off in the pressuresupport mode.
 15. The method of claim 14 wherein adjustment of flowthreshold is effected by fixed step increases or decreases in saidthreshold with polarity of said step changes being determined bypolarity of the T_(I) error signal.
 16. The method of claim 14 whereinadjustment of flow threshold is effected by variable step increases ordecreases in said threshold with magnitude of said variable step changesbeing determined by magnitude of T_(I) error signal and the estimatedrate of change in flow in the terminal part of the ventilators inflationphase.
 17. The method of claim 14 wherein flow threshold for cycling offis adjusted based on the magnitude of a composite signal consisting ofthe T_(I) error signal and/or the integral of the T_(I) error signaland/or the derivative of the T_(I) error signal.
 18. The methods of anyone of claims 1-16 or 17 wherein changes in ventilator T_(I) resultingfrom application of said methods are automatically accompanied bychanges in the delivered flow rate (in volume-cycled ventilation) or indelivered pressure support (in pressure support ventilation) intended topartially or completely offset the expected change in delivered tidalvolume.
 19. The method of claim 1 wherein the physiological range isfrom 0.25 to 0.50.
 20. A device for automatic ongoing adjustment of thecycling-off time of ventilator inflation phase during assistedventilation in accordance with true respiratory rate of the patient,comprising: circuitry for generating electrical signal(s) correspondingto the flow exchanged between patient and ventilator (flow) and/or toairway pressure (P_(aw)); digital or analog circuitry means fordetermining true respiratory rate of patient (patient RR) on an ongoingbasis from said flow and/or P_(aw) signals; digital or analog circuitrymeans for estimating current average cycle duration of patientrespiratory efforts (current patient T_(TOT)) from said patient RR;digital or analog circuitry means for calculating a current desirableduration of the inhalation phase (desirable T_(I)) from the product ofcurrent patient T_(TOT) and a T_(I)/T_(TOT) ratio chosen to be in aphysiological range; and means to cycle off ventilator inflation phasein accordance with said desirable T_(I).
 21. The device of claim 20wherein ongoing patient RR is estimated from the sum ofpatient-triggered ventilator cycles, ineffective efforts duringexhalation and additional efforts during the ventilator's inflationphase.
 22. The device of claim 21 wherein ineffective efforts areestimated from the derivative of the flow signal (Δflow/Δt), andidentifying negative transients in said signal that meet specifiedduration criteria, and/or from the derivative of the P_(aw) signal(ΔP_(aw)/Δt) and identifying positive transients in said signal thatmeet specified duration criteria.
 23. The device of claim 20 whereinongoing patient RR is determined from a composite signal incorporatingboth flow and P_(aw) signals.
 24. The device of claim 20 wherein ongoingpatient RR is determined by spectral analysis of the flow and/or P_(aw)signal.
 25. The device of claim 20 wherein ongoing patient RR isdetermined from electrical inductance or impedance of the chest wall,strain gauges placed on chest wall, or from signals measuring electricalactivity of respiratory muscles.
 26. The device of claim 20 whereinperiods of central apnea are excluded when estimating patient RR andpatient T_(TOT).
 27. The device of claim 20 wherein a minimum and/ormaximum limit is placed on the calculated desirable T_(I).
 28. Thedevice of claim 20 wherein the T_(I)/T_(TOT) ratio to be used incalculating desirable T_(I) is a user input.
 29. The device of claim 20wherein the T_(I)/T_(TOT) ratio to be used in calculating desirableT_(I) is a default value or a default function of patient RR.
 30. Thedevice of claim 20 wherein calculated desirable T_(I) is used todirectly determine the duration of the inflation phase of the ventilator(ventilator T_(I)).
 31. The device of claim 30 wherein ventilator T_(I)is set to equal desirable T_(I) plus a specified amount or a specifiedpercent.
 32. The device of claim 20 wherein actual T_(I) is alsodetermined in a number of recently elapsed breaths from the differencebetween cycling off time and either trigger time or time of onset ofinspiratory effort, and a T_(I) error signal corresponding to thedifference between actual and desirable T_(I) is generated.
 33. Thedevice of claim 32 wherein said T_(I) error signal is used to adjust theflow threshold for cycling off in the pressure support mode.
 34. Thedevice of claim 33 wherein adjustment of flow threshold is effected byfixed step increases or decreases in said threshold with polarity ofsaid step changes being determined by polarity of the T_(I) errorsignal.
 35. The device of claim 33 wherein adjustment of flow thresholdis effected by variable step increases or decreases in said thresholdwith magnitude of said variable step changes being determined bymagnitude of T_(I) error signal and the estimated rate of change in flowin the terminal part of the ventilator's inflation phase.
 36. The deviceof claim 33 wherein flow threshold for cycling off is adjusted based onthe magnitude of a composite signal consisting of the T_(I) error signaland/or the integral of the T_(I) error signal and/or the derivative ofthe T_(I) error signal.
 37. The devices of any one of claims 20-35 or 36wherein changes in ventilator T_(I) resulting from application of saidmethods are automatically accompanied by changes in the delivered flowrate (in volume-cycled ventilation) or in delivered pressure support (inpressure support ventilation) intended to partially or completely offsetthe expected change in delivered tidal volume.
 38. The devices of anyone of claims 20-35 or 36 wherein values of any or all of ineffectiveefforts, additional efforts, patient RR, desirable T_(I), T_(I) error,and/or recommended flow threshold for cycling off, or recommended changethereof, are displayed to the user.
 39. The device of claim 20 whereinthe physiological range is from 0.25 to 0.50.